The overall objective of this project is to evaluate a particular model for chemical carcinogenesis and cocarcinogenesis for possible use as a predictive molecular assay for compounds causing or influencing induction of cancer. The model stems from our current work on the molecular basis of cocarcinogenesis in rat embryo cell cultures. We have found evidence to suggest that activation of a specific set of genes is required before neoplastic transformation can be induced in these cells by carcinogens. Certain nonmutagenic agents can activate these genes and thereby sensitize cells to the transforming action of mutagenic carcinogens. We will determine the response of various rat cells to known and suspected carcinogens, tumor promoters, and permissive cocarcinogens, in terms of: transformation-related gene activation, measured by nucleic acid hybridization; effects on neoplastic transformation, in terms of cell morphology and growth behavior; and somatic mutation rates, measured in two different genetic loci unrelated to transformation.